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The pharmacokinetics of sulfadimidine (SDM) and its N4-acetyl metabolite (N4SDM) were investigated after intravenous bolus injection of a single dose (200 mg/kg) of SDM in normal and diseased New Zealand white rabbits. The apparent distribution volume at steady state, total body clearance and elimination half-life of SDM in normal animals were 0.7 +/- 0.3 l/kg, 0.57 +/- 0.24 l/kg/h and 1.6 +/- 1.3 h, respectively. Of the administered dose, 62.1% was metabolized by N4-acetylation, and 12.7 +/- 1.1 and 2.8 +/- 1.8% of the dose was excreted as free drug by the kidney and gastrointestinal tract, respectively. The 'apparent' formation and elimination half-lives of N4SDM were 0.6 +/- 0.4 and 2.2 +/- 1.1 h, respectively. The metabolite was eliminated mainly by excretion through the kidney. There was no significant effect of acute pasteurellosis on the pharmacokinetics of either SDM or N4SDM in rabbits. 相似文献
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Simultaneous pharmacokinetic-pharmacodynamic (PK-PD) models of meperidine in Soats were established by utilizing the P3 wave of the cerebral evoked potentials as an analgesic measurement. An effect compartment linked to the central compartment was postulated in the models. The hypothetical drug amount in the effect compartment was related to the observed analgesia through the Hill equation. After intramuscular (i. m., n = 16) and intravenous (i. v., n = 13) dosing (5 mg/kg), the elimination rate constants of meperidine in the effect compartment ( K eO ) were 0.3744 ± 0.2546 and 0.1123 ± 0.0428 min-1 , drug concentrations in the effect compartment generating half maximal analgesia (EC(50) ) were 0.70 ± 0.33 and 0.41 ± 0.26 μg/ml, the maximal effects (Emax ) were 89.63 ± 15.63 and 85.92 ± 9.64%, and the Hill coefficients (S) were 2.61 ± 1.21 and 2.37 ± 1.15, respectively. K eO and EC(50) with i.m. dosing were significantly greater than with i.v. injection. However, administration route had no influence on S, Emax and the total amount of effect ( AUE ). The predicted peak effect (Emax ^) of 64.44 ± 14.64 and 66.02 ± 11.51% were achieved at 14.7 ± 7.4 and 8.5 ± 2.2 min after i.m. and i.v. dosing, respectively. Peak analgesia appeared much later than peak plasma concentration, but simultaneously with peak CSF level both after i.m. and i.v. dosing. An obvious hysteresis was demonstrated between plasma concentration and analgesic effect. This study demonstrates that meperidine analgesia can be predicted using a PK-PD model, but not by PK data alone. Both i.m. and i.v. administration routes were evaluated kinetically and dynamically. 相似文献
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Qiao, G.-L., Fung, K.-F. Pharmacokinetic-pharmacodynamic modelling of meperidine in goats (I): pharmacokinetics. J. vet. Pharmacol. Therap. 16 , 426–437. Plasma and cerebrospinal fluid (CSF) pharmacokinetics of meperidine were investigated after intramuscular (i.m.) or intravenous (i.v.) administration at a dose of 5 mg/kg in adult goats. After i.m. dosing, the plasma profile was best described by a one-compartment open model. In healthy (n = 16) and postoperative (n = 16) goats, the parameters were, respectively: /max 8.3 ± 3.9 and 9.2 ± 5.5 min, Vd 2.763 ±1.231 and 3.929 ±2.101 1/kg, Clb 0.125 ± 0.036 and 0.087 ± 0.025 1/kg/min, Kc 0.0563 ± 0.0358 and 0.0271 ± 0.0136 min-1. The plasma profile was best fitted by a two-compartment open model following i.v. injection. In this case, the parameters for healthy (n= 7) and post-operative (n= 13) goats were, respectively: Vd 5.212 ± 1.992 and 5.085 ± 2.288 1/kg, Clb 0.096 ± 0.028 and 0.075 ± 0.026 1/kg/min, P 0.0211 ± 0.0093 and 0.0160 ± 0.0052 min.-1. There were, however, a few individuals with a prolonged elimination phase. Bioavailability of i.m. meperidine was 66.5 ± 15.8% in healthy (n= 6) goats, but much higher in postoperative (n = 10) ones at 94.6 ± 30.0%. Meperidine diffused into and out of CSF according to a first-order rate process. The time-course of CSF drug concentration was simulated by a biexponential function. CSF kinetic parameters of i.m. meperidine for healthy (n = 7) and postoperative (n = 13) goats were: elimination rate constant (Kei) 0.0269 ± 0.0131 and 0.0305 ± 0.0177 min“1, peak CSF concentration time (Tnaxl) 15.9 ± 5.0 and 17.0 ± 6.9 min. For the i.v. dosed healthy (n = 6) and postoperative (n = 8) animals, Kel was 0.0408 ± 0.0107, 0.0414 ± 0.0123 min-1 and 7maxt was 10.0 ± 5.0 and 7.7 ± 2.5 min, respectively. It was demonstrated that an obviously lower peak concentration can be reached significantly later in CSF than in plasma, and the kinetic behaviour of meperidine in plasma is different from that in the CSF, indicating meperidine analgesia might not be predicted by simple extrapolation from the kinetic data. 相似文献
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2006年5月,对贵州中部的鹭鸟群巢进行了调查,共记录到11个繁殖群、1587巢,种类包括小白鹭(Egretta garzetta)、牛背鹭(Bubulcus ibis)、池鹭(Ardeola bacchus)、夜鹭(Nycticorax nycticorax)和苍鹭(Ardea cinema).最大的繁殖群在黄平风云崖和赤水宴府.种类以小白鹭为优势种,其巢数量占总巢数的49.7%;而苍鹭最少,仪占0.1%.所有鹭鸟巢均只发现于贵州中、北部,而南部的雷公山地区没有调查到.鹭鸟群巢在贵州中部的分布明显受到农田种植模式(冬天种植小麦和油菜,夏天种植水稻)的影响,繁殖巢主要分布于稻作区.但在贵州南部的主要稻作区却没有发现鹭鸟繁殖群巢,其原因尚待调查.对贵州黄平和赤水这两个较大鹭鸟群巢所在地需重点加以保护. 相似文献
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The pharmacokinetics of potassium penicillin G were studied in both healthy (n = 8) and experimentally Streptococcus-suis-infected (n = 6) pigs following intramuscular administration (15,000 iu/kg). Streptococcus-suis infection was induced artificially in young cross-bred pigs by subcutaneous inoculation with 9 x 10(8) to 10(9) colony-forming units of S. suis. The rectal temperature of infected pigs was significantly increased (P less than 0.01) before penicillin G injection and this was maintained for 8 h after the drug was given. Other clinical symptoms were also present. The serum concentration-time data for penicillin were found to fit a one-compartment open model with first-order absorption in the two groups of pigs. Significant changes were not observed between healthy and diseased pigs in following parameters: A, Ka, Ke and Tmax. However, in diseased pigs, significant increases (P less than 0.01) were found in Vd and ClB, and significant decreases (P less than 0.01) in Cmax and AUC occurred. The increased body clearance (ClB) and greater apparent volume of distribution (Vd) of penicillin G could partly explain why the serum values of the drug were much lower in diseased pigs than in healthy pigs. 相似文献
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